SEPT9_V1 protein expression is associated with human cancer cell resistance to microtubule-disrupting agents

Cancer Biol Ther. 2007 Dec;6(12):1926-31. doi: 10.4161/cbt.6.12.4971. Epub 2007 Sep 1.

Abstract

SEPT9 is a mammalian septin family member. There is growing evidence that SEPT9 plays a role in cancer. The protein product, SEPT9_V1, associates with microtubules and interacts with hypoxia-inducible factor (HIF)-1alpha, the regulated subunit of the key transcription factor HIF-1. HIF-1 transcriptional activity is thoroughly dependent on intact microtubules. We tested the hypothesis that SEPT9_V1 confers resistance to microtubule-mediated HIF-1 inhibitors. SEPT9_V1 protein expression was strongly correlated with susceptibility of a wide range of cancer cells to 2-methoxyestradiol and paclitaxel. Our results revealed that SEPT9_V1 could serve as a biomarker for therapeutic resistance to microtubule disrupting agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 2-Methoxyestradiol
  • Antineoplastic Agents / pharmacology*
  • Benzoquinones / pharmacology
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Drug Resistance, Neoplasm / physiology*
  • Estradiol / analogs & derivatives*
  • Estradiol / pharmacology
  • GTP Phosphohydrolases / biosynthesis
  • GTP Phosphohydrolases / genetics
  • GTP Phosphohydrolases / physiology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / physiology
  • Indazoles / pharmacology
  • Lactams, Macrocyclic / pharmacology
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Paclitaxel / pharmacology*
  • Protein Isoforms
  • RNA Interference
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • RNA, Neoplasm / biosynthesis
  • RNA, Neoplasm / genetics
  • Recombinant Fusion Proteins / physiology
  • Septins
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / physiology
  • Tubulin Modulators / pharmacology*

Substances

  • Antineoplastic Agents
  • Benzoquinones
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Indazoles
  • Lactams, Macrocyclic
  • Neoplasm Proteins
  • Protein Isoforms
  • RNA, Messenger
  • RNA, Neoplasm
  • Recombinant Fusion Proteins
  • Tubulin Modulators
  • 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
  • tanespimycin
  • Estradiol
  • 2-Methoxyestradiol
  • GTP Phosphohydrolases
  • SEPTIN9 protein, human
  • Septins
  • Paclitaxel